At present, the investigation of the secretory function of the stomach is carried out with the aid of either food or medicamental (chemical) stimulation. The food stimulation is both safe and convenient, but it cannot solve the basic diagnostic problem, i.e. to establish an adequate relationship between the functional state of the mucous membrane of the stomach and pathological-morphological changes therein, because there are a number of different internal and external factors, such as the quality and composition of food, the psychic state of the patient, and the situation in the laboratory during the gastric intubation, which affect the diagnosis. Besides, food stimulation does not make it possible to produce a maximum level of hydrochloric acid secretion in the stomach, which accounts for frequent diagnostic errors. In an attempt to solve the problem, chemical secretion stimulators were subsequently developed.
Today's chemical (medicamental) secretion stimulators include histamine, gastrin preparations (pentagastrin), and histalog (an analog of histamine). The selectivity of histamine is limited, so that in addition to gastric secretion, it produces a number of side effects in the patient, such as reddening of the skin, nausea, vomiting, headache, dizziness, bronchospasm, edema of the rima vocalis, hypotension, and shocks. In most cases, these side effects can be fully eliminated by introducing such traditional antihistamines as H.sub.1 -antagonists, including mepyramine, tavelgil and suprastin. For that reason, histamine is used for what is known as the histamine test only in hospitals and in a limited number of cases.
Pentagastrin is a synthetic analog of the gastrin hormone. As a rule, the first administration of pentagastrin brings about no complications. Taken in a sufficient dose, this preparation can produce a maximum level of secretion; however, being a polypeptide by nature, it can produce allergic and anaphylactic reactions as a result of repeated administrations. In addition, the effect of a single dose of this preparation does not last long, so that an objective assessment of a maximum hourly output of hydrochloric acid requires a prolonged drop phlebocylysis, which is only possible under hospital conditions. Another factor which somewhat limits the use of pentagastrin on a large scale is its comparatively high cost.
Of late, gastroenterologists have been increasingly interested in synthetic analogs of histamine, of which histalog (or betazol manufactured by Lilly of the United States) has found the most extensive application in clinical practice. Histalog is a pyrazole analog of histamine, i.e. 3-(5)-(2-aminoethyl)pyrazole. The intensity of its effect upon the cardiovascular system (hypotension) is 700 times as low as that of histamine, although histalog is only 70 times less effective than histamine as to its capability of stimulating gastric secretion. Parenteral administrations of histalog to humans in doses of 1 to 5 mg/kg result in a maximum secretory response of the stomach, whereas side effects are observed far less frequently than in the case of histamine, which accounts for an extensive clinical application of histalog (cf. C. E. Rosiere, M. J. Grossman, Science, 1951, 113, 651; J. B. Kirsner, W. L. Palmer, W. Ford, Gastroenterology, 1952, 20, 138; G. Feifel, W. Lorenz, A. Heimann, J. Worsching, Klin. Wschr, 1972, 50, 422). It is not yet absolutely clear why histalog acts selectively upon the stomach. It is believed that apart from its selectivity as to receptors of the stomach, histalog can release endogenous histamine (cf. W. Lorenz, G. Feifel, A. Schmal, M. Hutel, E. Werle, Klin. Wschr., 1970, 48, 314).
Histamine is thought to act upon different physiological systems of the human organism through specific receptors (cf. A. S. Ash, H. O. Schild, Br. J. Pharmac., 1966, 27, 427-439; J. W. Black, W. A. Ducan, C. J. Durant, C. R. Ganellin, Nature, 1972, 236, 385-390). Experiments carried out by the abovementioned scientists revealed two types of histamine receptors, H.sub.1 and H.sub.2, in the human organism. It has been established that secretory cells of the stomach, which produce hydrochloric acid, are stimulated through H.sub.2 -receptors. Keeping in mind that histamine is equally selective both to H.sub.1 - and H.sub.2 -receptors, SKF of the United States have synthetized preparations which display a selective action upon H.sub.2 -receptors. These compounds can produce H.sub.2 -effects of histamine and, above all, gastric secretion, but with far less pronounced side effects on the part of H.sub.1 -receptors. These compounds are direct derivatives of histamine, more specifically, derivatives of 5-alkyl-4-(2-aminoethyl)imidazole. Experiments on animals indicate that pharmacologically, 5-methylhistamine appears to be the most promising under clinical conditions (cf. British Pat. No. 1,341,376, and French Pat. No. 2,254,311).
Experimental investigation of pharmacological properties of the foregoing compounds has been continued to this day (cf. G. Bertaccini, M. Impicciatore, T. Vitali, Farmaco. Ed. Sci., 1976, No 12, 935-938). However, no mention is made in medical literature of clinical uses of these compounds as diagnostic stimulators of gastric secretion, so that it is hard to assess their practical value. It must be pointed out that all the abovementioned chemical stimulators of gastric secretion, namely, histamine, pentagastrin, histalog and 5-methylhistamine have a major disadvantage in common: under clinical conditions, they can only be administered parenterally (intramuscular, intravenous and subcutaneous administration); if introduced per os, they are inactivated by the liver and enzymes of the alimentary canal, so that no secretory effect is produced. This factor hinders a large-scale application of said compounds because they have to be administered by means of painful injections which worry the patients. In addition, injections require sterile instruments and qualified staff.